Candida albicans is a yeast present in mucous membranes of about 80% of human population and belongs frequently to the normal oral and intestinal flora of human.
Usually non-pathogenic, this yeast however, can become virulent in weakened organisms and may cause a fungal infection of the mucous membranes in gynecological areas called candidiasis or thrush when occurring in the mouth (James, et al., 2006, Andrews' diseases of the skin: clinical dermatology (10th ed.), Philadelphia: Saunders Elsevier. p. 308; Scully C, 2008, Oral and maxillofacial medicine: the basis of diagnosis and treatment (2nd ed.), Edinburgh: Churchill Livingstone, 191-199). About 75% of women worldwide contract once in their life vaginal candidiasis caused by C. albicans, and approximately 5% of women have recurrent episodes (Egan et al., 2000, Am. Fam. Physician, 62(5), 1095; Monif, 1985, Am. J. Obstet. Gynecol., 152(7), 935; Foxman B, 1990, Am. J. Public Health, 80 (3), 329; Geiger et Foxman, 1996, Epidemiology, 7(2), 182). Candida albicans is carried in the mouth of about 50% of the world population as a normal component of the oral microbiota. However, when Candida species become pathogenic and invade host tissues, oral candidiasis may occur. This change usually constitutes an opportunistic infection of normally harmless micro-organisms due to local (i.e. mucosal), or systemic factors altering the host immunity (Kerawala et al., (editors), 2010, Oral and maxillofacial surgery. Oxford: Oxford University Press. pp. 446, 447); Bouquot et al., 2002, Oral & maxillofacial pathology (2. ed), Philadelphia: W.B. Saunders. pp. 189-197). Three main clinical appearances of candidiasis are generally recognized: pseudomembranous, erythematous (atrophic) and hyperplastic (Samaranayake, 2009, Essential microbiology for dentistry (3rd ed), Edinburgh: Churchill Livingstone, 178-180, 247, 293-297). The severity of oral candidiasis is subject to great inter- and intra-individual variability, and infectious episodes can be recurrent (Rhodus, 2012, “Treatment of oral candidiasis.”. Northwest dentistry, 91 (2): 32-3).
Several reasons are reported to cause this infection including the use of immunosuppressive drugs, oral contraceptives, or steroids, a weakened or undeveloped immune system for example due to HIV/AIDS, mononucleosis, or metabolic illnesses like diabetes (Odds, 1987, “Candida infections: an overview”, Crit. Rev. Microbiol., 15 (1):1-5). Further conditions are linked to candidiasis such as cancer treatments, stress, pregnancy, and nutrient deficiency.
Vaginal yeast infections occur after introduction of new yeast into the vaginal area, or after increasing in the quantity of yeast already present in the vagina. The second event is often correlated to the quantity of normal bacteria. For example, when the normal, protective bacteria are eradicated by antibiotics, the yeast can multiply, invade tissues, and cause irritation of the lining of the vagina (vaginitis). Vaginal yeast infections may also occur as a result of injury to the inner vagina, such as after chemotherapy. Immunocompromised women develop also vaginal yeast infections more frequently than women with normal immunity. In extreme cases, these superficial infections of the skin or mucous membranes may enter the bloodstream and cause systemic Candida infections (Choo et al., 2010, A comparative histopathological study of systemic candidiasis in association with experimentally induced breast cancer, Oncology Letters, 1(1), p. 215-222).
Further, recurrent vulvovaginal candidiasis are quite common and difficult to treat (Ilkit et al., 2011, Critical reviews in microbiology, 37 (3), p. 250-61; Sobel, 2007, Lancet, 369 (9577): p. 1961-71). The reason how changes in the vagina trigger candidiasis, is unclear. It is supposed to be associated to a hormonal imbalance. In most cases, the cause of the hormonal changes is unknown. Possible risk factors have been identified including intake of antibiotics. The treatment with antibiotics can actually lead to eliminating the yeast's natural competitors for resources it often increases the severity of the condition (Bassetti et al., 2010, Critical Care, 14 (6), 244). Candida albicans possesses many virulence factors such as adhesion, biofilm formation, and morphological transformation. The first and necessary step in infection is adherence. Candida albicans is able of adhering to buccal, vaginal and intestinal epithelial cells as well as catheters, dental implants or artificial joints. Candida albicans adherence process was reported to involve a complex set of multiple mechanisms (Ollert et al., 1993, Infect. Immun., 61 (11), 4560).
Furthermore, as a polymorphic organism, Candida albicans has the ability to grow in a variety of morphological forms. These last ones range from unicellular budding yeast to true hyphae with parallel-sided walls and, in between these two extremes, it can exhibit a variety of growth forms that are collectively referenced pseudohyphae (Sudbery et al. 2004, Trends in microbiology, 12 (7), 317-324; Bennett et al., 2005, Annu. Rev. Microbiol., 59, 233-255). The ability to switch between yeast, hyphal and pseudohyphal morphologies is often considered to be necessary for virulence, although formal proof remains lacking.
To date, several treatments are able to stop the rapid growth of C. albicans. They include intravaginal treatment with creams containing miconazole or econazole, two imidazoles which inhibit the biosynthesis of ergosterol, a component of fungal membranes. However, these molecules sometimes cause side effects such as irritation to the vulva or bleeding. Oral treatments with fluconazole are said to possess the same efficiency as intravaginal treatments, but are not recommended for pregnant women. Further, fluconazole has been reported to potentially cause severe allergic skin or hepatic reactions (Rossi (editor), 2006, Australian medicines handbook 2006, Adelaide: Australian Medicines Handbook; FDA Drug Safety Communication, Aug. 3, 2011: Use of long-term, high-dose Diflucan (fluconazole) during pregnancy may be associated with birth defects in infants) and present stability problems in water solution at ambient temperature (Dentinger et al., 2009, Ann. Pharmacother., 43(3), 485-489).
The genus Epilobium sp. (Onagraceae) consists of about 200 species worldwide. In Europe, this genus has about 28 species. Most species are commonly known as “Willow herb”. Tea and ethanolic extracts from aerial parts of this plant are used in folk medicine for the treatment of prostatic disorders, rheumatoid complaints, headache, and pain (Gruenwald et al., 2007, Physician Desk Reference for herbal medicines, (4th ed.), Montvale: Medical Economics Company, 903-4).
Therefore, there are important needs for new strategies of prevention and/or treatment of Candida infections, in particular recurrent Candida albicans infections.